Years of industry complaints appeared to pay off when the clock struck midnight on New Year’s Eve. FDA rang out 2012 with 39 approvals for new molecular entities—the second-highest number since 1996, when the agency approved Lipitor (atorvastatin) among 53 drug candidates.

“FDA is encouraged by the increase in NME approvals; but it’s too early to tell if it reflects a long-term trend,” FDA spokeswoman Lisa Kubaska, PharmD, told GEN.

Several factors explain the sharp increase from 30 drugs approved in 2011, and 21 in 2010; an average 23 new drugs were approved annually between 2002 and 2011. Those factors include FDA’s expanded options for faster new-drug reviews under the fifth authorization of the Prescription Drug User Fee Act (PDUFA V); more applications for new drug approvals, as big biopharma scrambles to recoup revenue lost as aging blockbusters lose patent protection; and jawboning by industry and investors that blamed the high cost of drug development on what they termed slow and complicated FDA reviews after the agency’s post-Vioxx shift toward more risk-benefit analysis.

While a final budget for the 2013 fiscal year has yet to be adopted, Dr. Kubaska said FDA is reviewing new drugs under PDUFA V, part of the FDA Safety and Innovation Act (FDASIA), enacted in July by President Barack Obama after sailing through Congress with rare bipartisan majorities.

FDASIA commits FDA to review and act on 90% of standard applications within 10–12 months from filing date, and on 90% of priority submissions within six to eight months from filing date. As of Nov. 30, all new drugs met PDUFA deadlines, with 81% approved in their first review cycle. However, FDASIA also pushed back the start of that first cycle to after the 60-day administrative filing review period.

New Breakthrough

FDASIA also created a new “breakthrough therapy” designation to speed up review of drugs intended “to treat a serious or life-threatening disease or condition, [where] preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.”

FDASIA also expanded fast-track products to include “qualified infectious disease products” such as new antibacterial drugs and drugs for rare diseases, as well as new drugs that, alone or with one or more drugs, are intended to treat serious or life-threatening diseases or conditions.

“FDA cannot expect a continuing upward trend for NME approvals until a sustained increase in the number of applications is also demonstrated,” added Dr. Kubaska, a lieutenant commander in the U.S. Public Health Service Commissioned Corps.

Rick Edmunds, senior partner and global health practice leader with Booz & Co., told GEN that while he is unsure whether drug approvals can continue rising annually, the increases seen until now stem from drug companies rebuilding their portfolios to make up for patent-cliff losses.

“I think it’s the direct result of the shift in portfolio strategy by most pharma over the past five-plus years. Specifically, you’re seeing more focus on specialty-oriented products, where the needs are much more fundamental unmet needs, rather than incremental or even reasonably significant clinical improvement in primary care, broad patient-based products,” Edmunds said.

One example of that focus: Of the 39 new drugs, 12 are for rare diseases. Eleven rare-disease drugs were approved in 2011.

Secondly, Edmunds said, drug developers have been more diligent in how they approach advancing products through FDA reviews: “Anything they thought could get approved, or had a shot at getting approved, they were pushing forward a few years ago because their pipelines were so bare. I think increasingly you’re seeing that having done some earlier weeding out, the products they’re bringing in they have more confidence in, in terms of market.”

“I think part of that is that the industry is in that area, doing a lot of R&D in oncology. But it’s also that the FDA is doing more to ensure that those products actually reach the marketplace,” Kenneth I. Kaitin, Ph.D., professor and director of the Tufts Center for the Study of Drug Development at Tufts University School of Medicine, told GEN.

As late as about three years ago, Dr. Kaitin recalled, FDA’s cancer division was under fire for what industry deemed were too-onerous requirements for getting a new cancer drug on the market: “They don’t look like the same division any more. There have been lots of oncology products that have been approved relative to the total number of product approvals this year and last year.”

Pulmonary and respiratory diseases—Eight drugs approved, including the first tuberculosis drug approved in four decades, Sirturo (bedaquiline) by Johnson & Johnson’s Janssen Therapeutics unit; and Vertex Pharmaceuticals’ Kalydeco (ivacaftor) for cystic fibrosis with the G551D mutation in the CFTR gene, the first CFTR potentiator.

Mixed and Slower

“If you’re in cancer or infectious diseases or if you’ve got an orphan drug, the agency is using pretty much all the tools at its disposal to move along those reviews and approvals. But in other areas—diabetes, endocrinology, CMS—the performance is much more mixed and slower,” David L. Gollaher, Ph.D., president and CEO of the California Healthcare Institute (CHI), told GEN.

CHI, which represents California’s biomedical industry, joined the Boston Consulting Group (BCG) in May to issue a report concluding that despite FDA efforts to shorten reviews, the agency took longer to approve drugs for diseases and conditions posing serious public health threats—including cardiovascular disease, obesity, and diabetes—than for cancer, hepatitis C, lupus, pneumonia, and orphan diseases.

During 2012, FDA approved three cardiovascular drugs, and one diabetes drug—Eli Lilly’s Jentadueto (linagliptin plus metformin hydrochloride) for type II diabetes. But the agency also okayed the first two weight loss drugs in more than a decade, Vivus’ Qsymia (phentermine and topiramate extended-release) and Belviq (lorcaserin hydrochloride), made by Arena Pharmaceuticals and distributed by Japan’s Eisai.

“Taken as a whole, the FDA has remained committed to getting important new products to the marketplace,” Dr. Kaitin said.

A key to that commitment, he said, was the series of PDUFA laws under which drug developers are charged “user fees” through which FDA funds new drug reviews. Every five years since 1992, PDUFA laws have sought to balance industry interests with FDA’s traditional interests in ensuring drug safety and efficacy.

“These issues that tended to fester over a long time, they really can’t anymore,” Dr. Kaitin said. “I don’t see a return the way we had in the past, where we went from 1962 to 1992 with an overly cautious, difficult to deal with, often confrontational regulatory agency.”

PDUFA laws alone won’t ensure smoother sailing for drug developers. As FDA likes to say, it can’t approve applications that don’t exist. That puts the burden on industry to continue developing drug candidates capable of withstanding agency scrutiny. But as Barry I. Eisenstein, M.D., senior vp, scientific affairs with Cubist Pharmaceuticals, correctly noted to GEN last month, all therapeutic areas are struggling with a greater degree of difficulty in finding new leads for breakthrough therapeutics.

“The modern genomic era, which 15 years ago we thought was going to allow for breakthroughs in a rapid way, has still not yet evolved to the point where it’s demonstrating that degree of proficiency in getting new leads,” Dr. Eisenstein said.

Until that improves, FDA is unlikely to see the sustained increase in new applications needed so it can approve more new drugs in coming years.

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